Registration Dossier

Administrative data

Description of key information

Oral 
LD50 rat: ca. 7900 mg/kg bw (Deichmann 1941)
Inhalation
LC50 rat, 4 h exposition: 29.8 mg/L (Tansy et al. 1980)
Dermal
LD50 rat, 24 h, occlusive conditions: >5000 mg/kg bw (Rohm & Haas 1982)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
no guideline followed
Principles of method if other than guideline:
Study to assess the acute oral toxicity of the test substance in rats before guideline development.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Supplier: Rohm & Haas Company, Philadelphia, Pensylvania
Inhibition:free of inhibitor to prevent polymerisation
Specific gravity: 0.936 @ 20 °C
Boiling point: 100-101 °C
Refractive index: 1.143 @ 20 °C
Species:
rat
Strain:
other: albino
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: own breeding
- Housing: Individual cages were used for housing rabbits and guinea pigs.
- Diet: rigidly controlled diet of Purina Rabbit or Fox Chow
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
no data
Doses:
8420, 9360, 10300 and 11230 mg/kg bw (corresponding to 9 - 12 mL/kg bw and 0.084 - 0.112 mol/kg bw, respectively)
No. of animals per sex per dose:
10 animals of unknown sex per dose
Control animals:
no
Details on study design:
Of the surviving animals, some were killed about a week after the treatment and studied for pathological tissue changes. All animals that died were examined.
Statistics:
LD50 values were calculated by the method of Bliss (1938).
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
ca. 7 900 mg/kg bw
Based on:
test mat.
Remarks on result:
other: corresponding to 8.41 mL/kg bw
Mortality:
8420 mg/kg bw: 6/10 animals died 7 to 80 hrs after application
9360 mg/kg bw: 7/10 animals died 8 to 40 hrs after application
10300 mg/kg bw: 10/10 animals died 8 to 24 hrs after application
11230 mg/kg bw: 9/10 animals died 8 to 32 hrs after application
Clinical signs:
Lethal doses produced a constant train of disturbances. The animals showed an increased rate of respiration (with lacrimation in rats) in  about 2 to 5 minutes, followed by motor weakness and decreased respiration in 15 - 40 minutes. Subsequently, respiration became shallow, irregular and labored and there were increased defecation and urination. Reflex activity was lost and the animals died in coma. The rats urine usually contained blood.
Body weight:
not measured
Gross pathology:
not reported
Interpretation of results:
GHS criteria not met
Conclusions:
LD50 rat: 7900 mg/kg
Executive summary:

In an oral toxicity study (Deichmann 1941) in Sprague Dawley rats methyl methacrylate 4 dose groups with each 10 animals where exposed to doses from 8.42 to 11.23 g/kg bw.

LD50 was 7900 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
7 900 mg/kg bw
Quality of whole database:
Oral
Results of various studies indicate a very low acute toxic potential of methyl methacrylate for the most common test species after oral application: the lowest valid LD50 values were 7900 mg/kg bw and 9400 mg/kg bw in rats (Deichmann 1941; Spealman 1945).
The studies were performed before GLP and OECD guidelines were established and therefore only basic data were available. However, they are broadly consistent with data obtained in other species and with other esters in the category of lower alkyl methacrylate esters and, therefore, the entire data base provided sufficient information to assess the acute oral toxicity.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given.
Principles of method if other than guideline:
Study to assess the acute inhalative toxicity of methyl methacrylate in rats after 4 h of exposure.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
not specified in the publication
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Diet (e.g. ad libitum): Purina Laboratory Chow
- Water (e.g. ad libitum): tap water
- Acclimation period: at least one week
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
75 liter glass dynamic chambers were used. The generation of the test atmosphere was previously described by Tansy et al., Environ. Res., 11:66, 1976.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
0 (sham exposed), 4750, 6146, 8044, 10209, 13479 ppm (corresponding to ca. 19.5, 25.2, 33.0, 41.9 and 55.3 mg/L)
No. of animals per sex per dose:
10 (5 males, 5 females)
Control animals:
yes
Details on study design:
24 hour post-exposure observation period.
Statistics:
Interpolation of the linear regression of the log of the number of survivors against concentration of vapor. The LC50 was computed from responses of those groups where the mortality was greater than zero and less than 100%.
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
29.8 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: corresponding to 7093 ppm
Remarks:
LC50 value coputed from responses of those groups where the mortality was greater than zero and less than 100 %
Mortality:
19.5 mg/L (4750 ppm): 8/10 animals died
25.2 mg/L (6146 ppm): 6/10 animals died
33.0 mg/L (8044 ppm): 2/10 animals died
41.9 mg/L (10209 ppm): 0/10 animals died
55.3 mg/L (13479 ppm): 0/10 animals died
Clinical signs:
other: not reported
Body weight:
not reported
Gross pathology:
not reported
Interpretation of results:
GHS criteria not met
Executive summary:

Acute inhalation toxicity of methyl methacrylate was tested in Sprague Dawley rats with 4 hours whole body exposure. 5 dose groups of 10 animals each (5males, 5 females) were tested in cocentrations of 19.5 mg/l (4750 ppm) to 55.3 mg/l (13476 ppm).

LC50 acute: 29.8 mg/l ( 7093 ppm). (Result based on those dose groups where result was greater than zero and less than 100 % mortality.)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
29 800 mg/m³
Quality of whole database:
The acute toxic potential of methyl methacrylate after inhalation exposure in rats is low (LC50 = 29.8 mg/L 4 h exposure; corresponding to 7093 ppm; Tansy et al. 1980)
 
The study was performed before GLP and OECD guidelines were established and therefore only basic data were available. However, they are broadly consistent with data obtained in other species and with other esters in the category of lower alkyl methacrylate esters and, therefore, the entire data base provided sufficient information to assess the acute inhalation toxicity.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Purity: 99.8% MMA
10 ppm Topanol A (12,4-Dimethyl-6-tert-butylphenol)
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.55 - 2.8 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
REMOVAL OF TEST SUBSTANCE
After the 24-h exposure, the cuffs were removed and the application sites were gently wiped with paper towels to remove the test substance. Despite this procedure, some of the test substance remained on the skin and fur staining them yellow. Subsequently animals were observed preening areas of treated skin.
Duration of exposure:
24 hrs
Doses:
0.2, 2.0 and 5.0 g/kg
No. of animals per sex per dose:
two males per dose
Control animals:
no
Details on study design:
Animals were observed 14 days post-dosing
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
There were no deaths observed
Clinical signs:
There were no clincial signs observed
Body weight:
not reported in full detail
Gross pathology:
There were no gross necropsy changes observed
Other findings:
There was well defined to severe erythema with blanching, and moderate to severe edema with pocketing were observed at 24 hr at one or more dose levels. Skin irritation did not disappear at 14 d at 2 or 5 g/kg but did disappear at day 3 at 0.2 g/kg. Eschar was observed at day 2 at 2 and 5 g/kg but some eschar was observed to be sloughing off with new hair growth on the underlying skin at day 2 at both dose levels. Dessication was observed after day 4 at all dose levels.
Interpretation of results:
GHS criteria not met
Executive summary:

In a dermal acute toxicity study with male New Zealand White rabbits animlas were tested in three dose groups (2 animals each) and treated with 0.2; 2.0 and 5.0 g/kg methyl methacrylate occlusive for 24 hours. No animals died in the tests.

LD50 acute dermal: > 5000 mg/kg

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
There is one valid study available reporting a LD50 value in rabbits comparable to OECD guideline 402 (Rohm & Haas 1982). The undiluted test substance was applied to the clipped skin of two New Zealand White rabbits per dose for 24 h under occlusive conditions. Even under these harsh conditions, no mortality, clinical signs or pathological findings were observed and the LD50 was therefore assessed to be >5000 mg/kg bw.
The study was performed before GLP and OECD guidelines were established and therefore only basic data were available. However, they are broadly consistent with data obtained in other species and with other esters in the category of lower alkyl methacrylate esters and, therefore, the entire data base provided sufficient information to assess the acute dermal toxicity.

Additional information

Other routes. There are studies for toxicity using other routes of exposure (i.p.,) using different species which are not considered being relevant for the assessment.

 

Justification for classification or non-classification

Based on the results of the available studies, methyl methacrylate is not required to be classified for its acute toxicity potential according to Regulation (EC) 1272/2008 requirements.

Under UN-GHS, MMA falls into category 5 for acute inhalation toxicity - with no classification for the dermal and oral routes.